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[ CAS No. 7498-57-9 ] {[proInfo.proName]}

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Product Details of [ 7498-57-9 ]

CAS No. :7498-57-9 MDL No. :MFCD00004122
Formula : C12H9N Boiling Point : -
Linear Structure Formula :- InChI Key :LPCWDVLDJVZIHA-UHFFFAOYSA-N
M.W : 167.21 Pubchem ID :82008
Synonyms :

Calculated chemistry of [ 7498-57-9 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.08
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 53.47
TPSA : 23.79 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.37 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.92
Log Po/w (XLOGP3) : 2.75
Log Po/w (WLOGP) : 2.91
Log Po/w (MLOGP) : 2.76
Log Po/w (SILICOS-IT) : 3.31
Consensus Log Po/w : 2.73

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.11
Solubility : 0.129 mg/ml ; 0.000772 mol/l
Class : Soluble
Log S (Ali) : -2.9
Solubility : 0.208 mg/ml ; 0.00125 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.56
Solubility : 0.00465 mg/ml ; 0.0000278 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.0

Safety of [ 7498-57-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280 UN#:N/A
Hazard Statements:H302+H312+H332 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 7498-57-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 7498-57-9 ]

[ 7498-57-9 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 98-03-3 ]
  • [ 7498-57-9 ]
  • (Z)-2-(naphthalen-2-yl)-3-(thiophen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 8 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
With ethanol unter Zusatz von wss. Kalilauge;
  • 2
  • [ 26421-44-3 ]
  • [ 7498-57-9 ]
  • 3<i>c</i>-(2,5-dimethyl-[3]thienyl)-2-[2]naphthyl-acrylonitrile [ No CAS ]
  • 3
  • [ 5381-20-4 ]
  • [ 7498-57-9 ]
  • 3<i>c</i>(?)-benzo[<i>b</i>]thiophen-3-yl-2-[2]naphthyl-acrylonitrile [ No CAS ]
  • 4
  • [ 7498-57-9 ]
  • [ 2017-68-7 ]
  • bis-(2-[2]naphthyl-ethyl)-amine [ No CAS ]
  • 6
  • [ 7498-57-9 ]
  • [ 109-94-4 ]
  • [ 51074-11-4 ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Glovebox; Schlenk technique; Inert atmosphere; Stage #2: formic acid ethyl ester In tetrahydrofuran at 20℃; for 12h; Glovebox; Schlenk technique; Inert atmosphere;
61% With sodium hydride In tetrahydrofuran; mineral oil at 20 - 50℃; Inert atmosphere;
With potassium ethoxide
With sodium ethanolate In ethanol

  • 7
  • [ 7498-57-9 ]
  • [ 17985-72-7 ]
  • 1,1,4,4-Tetramethyl-3-[1-naphthalen-1-yl-meth-(E)-ylidene]-1,2,3,4-tetrahydro-benzo[1,2,5]azadisiline [ No CAS ]
  • 8
  • [ 7498-57-9 ]
  • [ 100-39-0 ]
  • [ 5681-33-4 ]
YieldReaction ConditionsOperation in experiment
40% With sodium hydride In 1,2-dimethoxyethane for 3h; Heating;
40% With NaH In 1,2-dimethoxyethane 8.1 (Step 1) (Step 1) Preparation of 2-(2-Naphthalenyl)-3-phenylpropionitrile To a refluxing solution of NaH (3.00 g, 75 mmol, 60% dispersion) in DME (150 mL) was added a solution of 2-naphthaleneacetonitrile (12.5 g, 75 mmol) and benzyl bromide (12.8 g, 75 mmol) in DME (75 mL) dropwise over 50 minutes. The resulting solution was kept at reflux for 3 hours and then cooled to room temperature. The volatiles were removed in vacuo and the residue was partitioned between Et2 O (100 mL) and H2 O (100 mL). The aqueous phase was washed with Et2 O (1*150 mL), the organics were dried (MgSO4) and concentrated in vacuo. This residue was purified by preparative HPLC (SiO2: gradient hexane/EtOAc) to give the title compound as a white solid (7.71 g, 40%). NMR (200 MHz, CDCl3): δ 7.82 (m, 3H), 7.75 (s, 1H), 7.55 (m, 2H), 7.21 (m, 6H), 4.18 (t, 1H, J=7 Hz), 3.25 (m, 2H).
  • 9
  • [ 7498-57-9 ]
  • [ 74-88-4 ]
  • [ 22250-78-8 ]
YieldReaction ConditionsOperation in experiment
59% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran; mineral oil for 1h; Inert atmosphere; 86a Example 86a - Synthesis of Compound No. 86a (fi?SV2-(naphthalen-2- yDpropanenitrile) An oven dried 2 neck 250 mL round bottom flask was charged with 2- naphthylacetonitrile (8.36 g, 50 mmol). The system was degassed and backfilled with N2. Dry THF (100 mL) was added followed by addition of NaH (60% dispersion in oil, 2.1 mg, 52.5 mmol). The orange suspension was allowed to stir for 30 minutes at room temperature. The flask was fitted with an addition funnel containing a solution of iodomethane (3.1 mL, 50 mmol) in 40 mL of dry THF. The iodomethane solution was added drop-wise over a period of 0.5 hours from an addition funnel. Upon addition, the solution was stirred for additional 0.5 hours. The red solution was quenched by the addition of a saturated ammonium chloride solution (15 mL). The contents of the flask were poured into a separatory funnel, extracted with EtOAc (3 X 20 mL), dried over MgS04, and evaporated onto celite. The celite was placed onto a silica gel column and was eluted with a 10% EtOAc in hexane solution. 5.31 g (29.3 mmol, 59%) of a white powder was collected. 1H NMR (400 MHz, CDCl3) δ 7.91 - 7.81 (m, 4H), 7.56 - 7.48 (m, 2H), 7.43 (dd, J= 8.5, 2.0 Hz, 1H), 4.07 (q, J= 7.3 Hz, 1H), 1.73 (d, J= 7.3 Hz, 3H).
With sodium amide 1.) Et2O, reflux, 1 h, 2.) Et2O, reflux, 1 h; Yield given. Multistep reaction;
  • 10
  • [ 7498-57-9 ]
  • [ 74-88-4 ]
  • [ 69849-14-5 ]
YieldReaction ConditionsOperation in experiment
99% With sodium hydride; sodium iodide In tetrahydrofuran; mineral oil at 85℃; for 7h; Inert atmosphere; Sealed tube;
93% With lithium diisopropyl amide In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃;
Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 0 - 20℃; for 13h; Inert atmosphere;
  • 11
  • [ 7498-57-9 ]
  • [ 2017-68-7 ]
YieldReaction ConditionsOperation in experiment
67% With aluminium trichloride; In water; Step A 2-naphthaleneethanamine Aluminum trichloride (7.6 g, 57 mmole) was added in portions to 30 mL of ether cooled to 0 C. under nitrogen. In a separate flask, lithium aluminum hydride (2.2 g, 57 mmole) was slurried in 30 mL of ether and cooled to -5 C. with an ice/acetone bath. The etherial aluminum trichloride solution was added dropwise to the LiAlH4 slurry at such a rate as to maintain a temperature of 0 C. Fifteen minutes after addition was complete, 2-naphthylacetonitrile (4.0 g, 24 mmole) in 40 mL of ether was added dropwise while maintaining a temperature of 0 C. The reaction mixture was stirred for an additional 15 minutes at 0 C. and then allowed to warm to room temperature for 1 hour. After recooling to 0 C., the reaction was quenched by careful dropwise addition of water. The mixture was diluted with ether, partitioned, and the aqueous phase was basified with 30% NH4 OH solution. Extraction of the aqueous phase with ether, combination of the organic phases, drying, and concentration gave a colorless oil (2.7g, 67% yield). 1 H MNR (CDCl3): delta 7.80 (m, 3H), 7.65 (s, 1H), 7.45 (m, 2H), 7.30 (m, 1H), 3.06 (t, 2H), 2.91 (t, 2H), 1.35 (s, 2H).
Arylethylamines that were not commercially available were made by the following procedure. 2-Naphthylacetonitrile Compound 3-2 (16.7 g, 0.10 mol) in anhydrous tetrahydrofuran (50 mL) was added to 1M solution of BH3-THF (250 mL, 0.25 mol) over 10 min at room temperature. The reaction proceeds with an induction period of 2-4 min. Following the addition, the mixture was heated under reflux and under argon for one hour (TLC of a quenched aliquot showed no starting material). The reaction was cooled in an ice bath and 10% aqueous HCl (150 mL) was added with caution over a 30 min period (vigorous reaction with the first few drops). Following the addition concentrated hydrochloric acid (100 mL) was added and the mixture brought up to reflux for 30 min. The reaction was cooled in an ice bath and extracted once with ethyl ether. The aqueous layer was carefully brought to pH 12 with 40% sodium hydroxide solution (use of concentrated base allows for smaller volumes of the aqueous layer and simplifies the extraction of the amine) and extracted with diethyl ether (4×250 mL). The organic layer was washed with brine (50 mL), dried over sodium sulfate, and evaporated at reduced pressure below 40 C. The solvent was not completely removed to avoid loss of product. TLC (85:15 CHCl3/MeOH, Rf=0.1) shows that the amine is essentially pure. Oxalic acid (9.0 g, 0.10 mole) was dissolved in methanol (10 mL) and added to the crude amine diluted with diethyl ether to a 300 mL volume. The white precipitate was collected by filtration, washed with ether, and dried in vacuo to provide Compound 3-3 (22.3 g, 85%) as the oxalate salt (mp=191-193 C.). Anal Calcd. for C12H13N-0.85 C2O4H2: C, 66.42; H, 5.98. Found: C, 66.67; H, 6.05. Compound 3-3 freebase: 1H NMR (300 MHz, CDCl3) delta 7.83-7.77 (m, 3H), 7.65 (s, 1H), 7.49-7.40 (m, 2H), 7.34 (d of d, J=8.5 and 1.6 Hz, 1H), 3.06 (t, J=7 Hz, 2H), 2.92 (t, J=7 Hz, 2H).
With borane-THF; nickel(II) chloride hexahydrate; In tetrahydrofuran; for 1h; Example 18 2-Naphth-2-ylethylamine Combine naphth-2-ylacetonitrile (1.0 g, 6.0 mmol) and nickel (II) chloride hexahydrate (0.7g, 3.0 mmol) and tetrahydrofuran (30 ml). Add dropwise boranetetrahydrofuran complex, 1M solution in tetrahydrofuran (24.0 ml, 24.0 mmol). After 1 hour, evaporate to give a residue. Chromatograph on silica gel eluting with 8:2 EtOAc:MeOH + 2% NH4OH) to give the title compound.
  • 12
  • [ 7498-57-9 ]
  • 5-(2-Naphthylmethyl)-1H-tetrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With hydrogenchloride; sodium azide; triethylamine In toluene at 110℃; General procedure for preparation of 5-substituted1-H-tetrazoles (2a-2m) General procedure: Nitriles (1 mmol) were added to a solution of NaN3 (3 mmol), PhMe (50 mL), and Et3N.HCl (3 mmol) in around-bottomed flask. The reaction mixture was stirred at 110 °C. After completion of the reaction (as indicated byTLC), the product was cooled and extracted with water. Next, 36% HCl was added dropwise to the aqueous layer to precipitate the tetrazoles. After filtration, the solid wasdried under reduced pressure and recrystallized fromEtOAc/Et2O to yield the 5-substituted-1-H-tetrazoles.
43% With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 135℃;
42% With sodium azide; cerium(III) chloride heptahydrate In water; isopropyl alcohol at 160℃; for 4h; Microwave irradiation; General Methodology for the Synthesis of 5-Substituted 1H-Tetrazoles General procedure: Synthesis of 5-(thiophen-3-yl)-1H-tetrazole (2a). 3-Thiophenecarbonitrile 1a (218 mg, 2 mmol), NaN3 (260 mg,4 mmol), CeCl3·7H2O (75 mg, 0.2 mmol), and 8 mL of a 3:1isopropanol/water mixture were added to a 30-mL Pyrexmicrowave vessel and capped. The microwave vessel wasthen placed in a multi-mode microwave reactor. The reactionwas magnetically stirred and heated for 1 hour at 160 °C.The pressure in the vessel was not determined. The reactionwas monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reactionmixture was diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (2 x 15 mL).The aqueous sodium bicarbonate layer was cooled with iceand acidified to a pH of 2 or less with concentrated hydrochloricacid, which was added drop-wise. The precipitateformed was extracted with ethyl acetate (3 x 15 mL). Thecombined organic layers were dried over anhydrous sodiumsulfate and decanted into a tared round bottom flask. Theorganic layer was concentrated under reduced pressure. Thetetrazole product was recrystallized from ethyl acetate andhexane. All reagents mentioned above were used unpurified.
  • 13
  • [ 7498-57-9 ]
  • [ 100-52-7 ]
  • (2RS,3RS)-3-hydroxy-2-(2'-naphthyl)-3-phenylpropionitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran for 1.25h; Inert atmosphere; Stage #2: benzaldehyde In tetrahydrofuran for 0.416667h; Inert atmosphere; 130 Example 130 - Synthesis of Compound ID No. 130 ((R2R or l£25 -2-(naphthalen- 2-yiy 1 -phenyl-3 -(2,2,2-trifluoroethylamino)propan- 1 -of) nft'-3-hydroxy-2-(naphthalen-2-yl)-3-phenylpropanenitrile: A 22-L three neck round bottom flask equipped with a mechanical stirrer, nitrogen inlet, thermometer, and addition funnel with septum was charged with THF (12 L) and diisopropylamine (0.180 L, 1260.28 mmol) and chilled to -78°C. N-butyllithium (0.490 L, 1224.28 mmol) was added and stirred for 5 minutes. A solution of 2- (naphthalen-2-yl)acetonitrile (206.9 g, 1.2 mol) in THF (2 L) was added drop-wise over 45 minutes and the resulting solution stirred for 30 minutes. Benzaldehyde (0.122 L, 1200.27 mmol) was added drop-wise over 5 minutes and stirred for an additional 20 minutes before the reaction was quenched by the addition of acetic acid (150 g) in THF (250 mL) at -72°C. The layers separated, and the aqueous layer was extracted with Et20 (2 x 1 L). The combined organic extracts were washed with brine (1 L), dried over MgS04j and concentrated in vacuo to give the crude product (379.6 g, 116%). Recrystallization from THF (640 mL) hexanes (800 mL) at 40°C gave 3- hydroxy-2-(naphthalen-2-yl)-3-phenylpropanenitrile (228 g, 69.4 %).Recrystallization with THF and hexane at 40°C gave 174 g (53%) anti isomer contaminated with about 5.2 g of the syn isomer. 1H NMR in CDC13 showed the presence of the expected structure.
With lithium diisopropyl amide 1) THF, -78 deg C; 2) THF, -78 deg C; Yield given. Multistep reaction;
With lithium diisopropyl amide 1.) -78 deg C, 2.) -78 deg C; Multistep reaction;
  • 14
  • [ 7498-57-9 ]
  • [ 7664-93-9 ]
  • [ 64-19-7 ]
  • palladium/charcoal [ No CAS ]
  • [ 2017-68-7 ]
  • 15
  • [ 37859-25-9 ]
  • [ 7498-57-9 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 2-naphthylacetyl chloride With oxalyl dichloride In benzene at 21℃; for 6h; Stage #2: With 2,4-dinitrobenzenesulfonamide; triethylamine In tetrahydrofuran for 24h; Heating;
60.38 g With sulfolane; SULFAMIDE In toluene at 95 - 105℃; for 4h; Inert atmosphere; 2-6 In another nitrogen-substituted reactor were added sulfamide (46.49 g) (1.2 mole ratio to 2-naphthylacetic acid), an inorganic additive (74.99 g) (1 weight ratio to 2-naphthylacetic acid), and sulfolane (263 mL) (3.5 volume ratio to 2-naphthylacetic acid), and the mixture was heated (preparation of reaction starting material 2). The reaction starting material 1 containing 2-naphthylacetyl chloride was added dropwise to the reaction starting material 2 at 95° C.-105° over 18 min. The instrument used for preparing the reaction starting material 1 was washed with toluene (7.5 mL) (0.1 volume ratio to 2-naphthylacetic acid), the obtained solution was further added to the reaction starting material 2, and the mixture was reacted at 95° C.-105° C. for 4 hr. The reaction mixture was analyzed by HPLC, and the disappearance of the starting materials was confirmed. Then, the mixture was cooled to 20° C.-30° C., water (300 mL) (4 volume ratio to 2-naphthylacetic acid) and toluene (300 mL) (4 volume ratio to 2-naphthylacetic acid) were added, the mixture was stirred, and the aqueous layer was discarded. The remaining organic layer was washed with 10 wt % potassium carbonate aqueous solution (225.08 g) (3 weight ratio to 2-naphthylacetic acid) and water (150 mL) (2 volume ratio to 2-naphthylacetic acid). The obtained organic layer was concentrated, methanol (525 mL) (7 volume ratio to 2-naphthylacetic acid) was added to the concentrated residue, and the mixture was concentrated again. Furthermore, methanol was added to the obtained concentrated residue to adjust the liquid amount to 525 mL. Activated carbon (1.52 g) (0.02 weight ratio to 2-naphthylacetic acid) was added, and the mixture was stirred at 50° C.-60° C. and filtered. The obtained filtration residue was washed with methanol (75 mL) (1 volume ratio to 2-naphthylacetic acid). The obtained filtrate and washing solution were cooled to 5° C.-15° C., water (300 mL) (4 volume ratio to 2-naphthylacetic acid) was added, and the mixture was stirred. The precipitated 2-naphthylacetonitrile was collected by filtration, and the obtained wet crystals were dried to obtain 2-naphthylacetonitrile (60.38 g) (purity 99.85 area %) as a solid.
  • 16
  • [ 615-83-8 ]
  • [ 7498-57-9 ]
  • [ 640724-29-4 ]
YieldReaction ConditionsOperation in experiment
55% Stage #1: 2-bromo-pentanoic acid ethyl ester; 2-naphthaleneacetonitrile With zinc In tetrahydrofuran for 1.16667h; Heating; Stage #2: With hydrogenchloride In tetrahydrofuran at 20℃; for 0.75h;
  • 17
  • [ 959842-57-0 ]
  • [ 7498-57-9 ]
YieldReaction ConditionsOperation in experiment
99% With hydrogen In ethyl acetate at 20℃;
  • 18
  • [ 581-96-4 ]
  • [ 7498-57-9 ]
YieldReaction ConditionsOperation in experiment
90% With sodium azide; TEA; triethylphosphine In dichloromethane; dimethyl sulfoxide at 0℃; for 40h;
Multi-step reaction with 2 steps 1: 72 percent / Et3N, PPh3-CBr4 / acetonitrile / 3 h / Heating 2: 80 percent / Na2CO3 / methanol / 2 h / Irradiation
Multi-step reaction with 2 steps 1.1: trichlorophosphate / 30 °C 1.2: 18 h / 70 °C 1.3: 16 h / 78 °C 2.1: potassium fluoride; water / methanol / 16 h / 90 °C
Stage #1: 2-naphthylacetic acid With sulfolane; thionyl chloride; SULFAMIDE at 95 - 105℃; for 7h; Inert atmosphere; Stage #2: With pyrographite In methanol at 0 - 60℃; Inert atmosphere; 2; 3; 4; 5; 5; 6; 7 Example 5: Synthesis of Nitrile Compound In a nitrogen-substituted reactor were placed 2-naphthylacetic acid (90.0 g) obtained in Example 2, sulfamide (51.1 g, 1.1 mole ratio to carboxylic acid compound), and sulfolane (315 mL, 3.5 volume ratio to carboxylic acid compound), and the mixture was stirred. The temperature was raised, and thionyl chloride (69.0 g, 1.2 mole ratio to carboxylic acid compound) was added at 95° C.-105° C. After reacting at 95° C.-105° C. for 7 hr, the reaction mixture was cooled, and activated carbon (Kyoryoku Shirasagi) (1.8 g, 0.02 weight ratio to carboxylic acid compound) and methanol (180 mL, 2 volume ratio to carboxylic acid compound) were added at 50° C.-60° C., and the mixture was stirred and filtered. The filtration residue was washed with methanol (90 mL, 1 volume ratio to carboxylic acid compound). The filtrate and the solution after washing were mixed, water (540 mL, 6 volume ratio to carboxylic acid compound) was added at 35° C.-45° C. The mixture was stirred, cooled to 0° C.-10° C., and precipitated 2-naphthylacetonitrile was recovered. The obtained 2-naphthylacetonitrile was 63.2 g, and the purity measured by HPLC (HPLC analysis conditions-3) was 99.5 Area %.The HPLC analysis results of the obtained 2-naphthylacetonitrile are shown in FIG. 8, and the 1H-NMR measurement results are shown in FIG. 9.
Multi-step reaction with 3 steps 1: thionyl chloride / toluene; N,N-dimethyl-formamide / 3 h / 40 °C / Inert atmosphere 2: ammonium hydroxide / 1 h / 50 °C 3: trichlorophosphate / toluene; n-heptane / 4 h / 85 °C / Inert atmosphere
With potassium carbonate 1.2 (2) The acid chloride solution was added dropwise to the sulfamide solution over 2 hr at 95° C.-105° C. The reactor that contained the acid chloride solution was washed with toluene (1.62 kg). The liquid obtained after washing was also added to the reactor, and the mixture was reacted at 95° C.-105° C. for 7 hr. The obtained reaction mixture was cooled to 25° C., toluene (65 kg) and water (74.8 kg) were added, the mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. To the remaining upper layer were added water (35.5 kg) and potassium carbonate (5.61 kg). The instrument used for the above-mentioned reaction was washed with water (15 kg) and the liquid obtained after washing was also added to a mixture containing the above-mentioned upper layer. The obtained mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. To the remaining upper layer was added water (37.4 kg), the mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. The remaining upper layer was concentrated, methanol (104 kg) was added, and the mixture was further concentrated. To the obtained concentrated liquid was added methanol (44.4 kg), and the mixture was concentrated. To the obtained concentrated liquid were added activated carbon (0.374 kg) and methanol (45.1 kg) at 35° C., and the mixture was stirred and filtered. The filtration residue was washed with methanol (14.95 kg), and the filtrate and the liquid after washing were mixed. The obtained mixed solution was maintained at 30° C.-40° C. for about 90 min and cooled, water (74.8 kg) (4 volume ratio to 2-naphthylacetic acid) was added at a temperature near 10° C., and the mixture was stirred for 4 hr. The precipitated crystals were collected by centrifugation, and the collected wet crystals were washed with a methanol aqueous solution (mixed solution of methanol (14.8 kg) and water (18.7 kg)). The obtained wet crystals were dried under reduced pressure under temperature condition at 60° C. to give 2-naphthylacetonitrile as crystals (15.2 kg, purity 99.50 area %). 1H-NMR (400 MHz, CDCl3) δ 3.92 (2H, s), 7.37-7.40 (1H, m), 7.49-7.54 (2H, m), 7.83-7.85 (4H, m)
15.2 kg Stage #1: 2-naphthylacetic acid With thionyl chloride; N,N-dimethyl-formamide In toluene at 35 - 45℃; for 5h; Inert atmosphere; Large scale; Stage #2: With sulfolane; SULFAMIDE In toluene at 95 - 105℃; for 7h; Inert atmosphere; Large scale; 1.2 (2) Synthesis of 2-naphthylacetonitrile In a nitrogen-substituted reactor were added 2-naphthylacetic acid (18.7 kg) obtained in the above-mentioned (1), toluene (40.55 kg), and N,N-dimethylformamide (73.08 g). The instrument used for the above-mentioned addition was washed with toluene (16.2 kg) and the liquid obtained after washing was also added to the reactor. To the obtained solution was added thionyl chloride (12.5 kg) (1.05 mole ratio to 2-naphthylacetic acid), and the mixture was reacted at 35° C.-45° C. for 5 hr. After cooling to 20° C.-30° C., the mixture was filtered. The obtained filtrate was mixed with a washing obtained by washing the filtration residue with toluene (8.15 kg), sulfolane (23.6 kg) (1 volume ratio to 2-naphthylacetic acid) was added, and the mixture was concentrated under reduced pressure to prepare an acid chloride solution. In another nitrogen-substituted reactor were placed sulfamide (11.6 kg) (1.2 mole ratio to 2-naphthylacetic acid), sulfolane (58.9 kg) (2.5 volume ratio to 2-naphthylacetic acid) and an inorganic additive (18.7 kg), and the mixture was stirred and heated to 95° C.-105° C. to prepare a sulfamide solution. The acid chloride solution was added dropwise to the sulfamide solution over 2 hr at 95° C.-105° C. The reactor that contained the acid chloride solution was washed with toluene (1.62 kg). The liquid obtained after washing was also added to the reactor, and the mixture was reacted at 95° C.-105° C. for 7 hr. The obtained reaction mixture was cooled to 25° C., toluene (65 kg) and water (74.8 kg) were added, the mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. To the remaining upper layer were added water (35.5 kg) and potassium carbonate (5.61 kg). The instrument used for the above-mentioned reaction was washed with water (15 kg) and the liquid obtained after washing was also added to a mixture containing the above-mentioned upper layer. The obtained mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. To the remaining upper layer was added water (37.4 kg), the mixture was stirred at 20° C.-30° C. and allowed to stand, and the lower layer was discarded. The remaining upper layer was concentrated, methanol (104 kg) was added, and the mixture was further concentrated. To the obtained concentrated liquid was added methanol (44.4 kg), and the mixture was concentrated. To the obtained concentrated liquid were added activated carbon (0.374 kg) and methanol (45.1 kg) at 35° C., and the mixture was stirred and filtered. The filtration residue was washed with methanol (14.95 kg), and the filtrate and the liquid after washing were mixed. The obtained mixed solution was maintained at 30° C.-40° C. for about 90 min and cooled, water (74.8 kg) (4 volume ratio to 2-naphthylacetic acid) was added at a temperature near 10° C., and the mixture was stirred for 4 hr. The precipitated crystals were collected by centrifugation, and the collected wet crystals were washed with a methanol aqueous solution (mixed solution of methanol (14.8 kg) and water (18.7 kg)). The obtained wet crystals were dried under reduced pressure under temperature condition at 60° C. to give 2-naphthylacetonitrile as crystals (15.2 kg, purity 99.50 area %).

  • 19
  • [ 2896-60-8 ]
  • [ 7498-57-9 ]
  • [ 906480-93-1 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-ethyl-1,3-benzenediol; 2-naphthaleneacetonitrile With hydrogenchloride; boron trifluoride diethyl etherate In diethyl ether for 12h; Stage #2: With hydrogenchloride; ethanol; water Heating / reflux; 2 Compound 2: 4-(Naphthalen-2-yl)-5-(2-hydroxy-4-methoxy-5-ethyl-phenyl)- isoxazole; To a mixture of 4-ethyl-benzene-1 ,3-diol (a, 10 mmol) and naphthalen-2-yl- acetonitrile (b, 10 mmol) in boron trifluoride etherate (20 ml_) was bubbled gaseous HCI for 12 h. The solids that formed were collected by filtration and heated in 6N HCI(100 mL) and EtOH (20 mL) for 6 h. The mixture was diluted with water and extracted with CH2CI2. The organic extract was washed with water and dried. The oil obtained on concentration of the organic layer was crystallized in EtOAc/hexanes to give 1-(5-ethyl-2,4-dihydroxy-phenyl)-2-naphthalen-2-yl-ethanone (c, 0.74g).
With hydrogenchloride; boron trifluoride diethyl etherate In ethanol; water at 90℃; for 18h; 1 To a mixture of 4-ethyl-benzene-l,3-diol (a, 10 mmol) and naphthalen-2-yl- acetonitrile (b, 10 mmol) in boron trifluoride etherate (20 mL) was bubbled gaseous HCl for 12 h. The solids that formed were collected by filtration and heated in 6N HCl (100 mL) and EtOH (20 mL) for 6 h. The mixture was diluted with water and extracted with CH2Cl2. The organic extract was washed with water and dried. The oil obtained on concentration of the organic layer was crystallized in EtOAc/hexanes to give 1 -(5-ethyl-2,4-dihydroxy-phenyl)-2-naphthalen-2-yl-ethanone (c, 0.74g).
  • 20
  • [ 7498-57-9 ]
  • [ 5787-31-5 ]
  • [ 64497-77-4 ]
YieldReaction ConditionsOperation in experiment
86% With sodium hydroxide In benzene 2 Preparation of α-sec-butyl-2-naphthaleneacetonitrile STR10 EXAMPLE 2 Preparation of α-sec-butyl-2-naphthaleneacetonitrile STR10 A mixture of 2-naphthaleneacetonitrile (30.00 g, 0.179 mole), dicyclohexyl-18-crown-6 [1.60 g, 0.0043 mole (2.4 mole %)], 2-bromobutane (50.20 g, 0.366 mole), benzene (80 ml) and sodium hydroxide solution (50%, 80 ml) is stirred at room temperature for 16 hours. The organic layer is diluted with ether (250 ml), separated, washed successively with water, dilute hydrochloric acid and water and dried over sodium sulfate. Evaporation and distillation under vacuum gives α-sec-butyl-2-naphthaleneacetonitrile (34.3 g, 86%); b.p. 130° C. (0.1 mm). Analysis calculated for C16 H17 N: C, 86.05; H, 7.68; N, 6.27. Found: C, 85.91; H, 7.76; N, 5.96.
86% With sodium hydroxide In benzene 2 Preparation of α-sec-butyl-2-naphthaleneacetonitrile STR6 EXAMPLE 2 Preparation of α-sec-butyl-2-naphthaleneacetonitrile STR6 A mixture of 2-naphthaleneacetonitrile (30.00 g, 0.179 mole), dicyclohexyl-18-crown-6 [1.60 g, 0.0043 mole (2.4 mole %)], 2-bromobutane (50.20 g, 0.366 mole), benzene (80 ml) and sodium hydroxide solution (50%, 80 ml) is stirred at room temperature for 16 hours. The organic layer is diluted with ether (250 ml), separated, washed successively with water, dilute hydrochloric acid and water and dried over sodium sulfate. Evaporation and distillation under vacuum gives α-sec-butyl-2-naphthaleneacetonitrile (34.3 g, 86%); b.p. 130° C. (0.1 mm). Analysis calculated for C16 H17 N: C, 86.05; H, 7.68; N, 6.27. Found: C, 85.91; H, 7.76; N, 5.96.
  • 21
  • [ 7498-57-9 ]
  • [ 292638-85-8 ]
  • dimethyl 3-cyano-3-(naphthalen-2-yl)hexanedioate [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 2-naphthaleneacetonitrile; acrylic acid methyl ester In <i>tert</i>-butyl alcohol Heating / reflux; Stage #2: With tetra(n-butyl)ammonium hydroxide In methanol; <i>tert</i>-butyl alcohol at 20℃; Heating / reflux; 4.2.1 2-naphthylacetonitrile (3.45 g, 20.6 mmol) and methyl acrylate (9.7 ml, 107 mmol) were suspended in 2-methyl-2-propanol (10 ml). Heat was applied to the reaction vessel until the solution became clear. The mixture was cooled to room temperature, at which time (Bu)4NOH (6.9 mmol, 0.33 equiv.) was added as a solution in 2-methyl-2-propanol:methanol (1 :2). The combined reaction mixture was heated to reflux for 4 h under vigorous stirring at which time the reaction appeared complete by GC-MS. After allowing the reaction to cool the mixture was partitioned between H2O (75 ml) and EtOAc (50 ml). The aqueous layer was removed and washed with EtOAc (2 x 50 ml). The combined organic phases were washed with NaHCO3 (sat. aq.) and brine and dried over MgSO4. After filtration the solvent was removed in vacuo. The crude product was purified by flash column chromatography (25% EtOAc in hexanes) to isolate the title compound as a light yellow oil (5.75 g, 82%).
  • 22
  • [ 7498-57-9 ]
  • [ 2043-61-0 ]
  • (2RS,3SR)-3-cyclohexyl-3-hydroxy-2-(2'-naphthyl)proiononitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% Stage #1: 2-naphthaleneacetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: cyclohexanecarbaldehyde In tetrahydrofuran for 0.5h; Stage #3: With hydrogenchloride; water; ammonium chloride more than 3 stages; 4 Example 4 Synthesis of (2R,3SR)-3-cyclohexyl-3-hydroxy-2-(2'-naphthyl)proiononitrile (2R,3SR)-3-cyclohexyl-3-hydroxy-2-(2'-naphthyl)propiononitrile (Compound 1; ) was made as follows. 2-Naphthylacetonitrile (1.49 g, 8.93 mmol, 1 eq) and 20 mL freshly distilled THF were placed in a 250 mL round-bottomed flask. After purging with N2, the solution was cooled to -78° C., and 2.0 M LDA solution (5.4 mL, 10.7 mmol, 1.2 eq) was added via syringe. The mixture was stirred for 30 minutes. Cyclohexanecarbaldehyde (1.3 mL, 10.7 mmol, 1.2 eq) was added via syringe, and the resulting mixture stirred for 30 minutes. Saturated NH4Cl (12 mL) was poured into the reaction flask at -78° C. After warming to room temperature, 20 mL 1 N HCl was added, and the aqueous layer was extracted with Et2O (4*25 mL). The combined organic extract was dried (MgSO4), filtered, stripped, and dried in vacuo. The crude aldol obtained was then washed with pet ether/ether (4 mL/2 mL) and recrystallized twice from hot toluene. Finally, 859 mg (34%) of the pure anti-aldol was recovered. 1H-NMR (CDCl3): δ 1.071-1.305 (m, 6H), 1.626-2.081 (m, 6H), 3.614 (dd, J=4.0 Hz, 7.4 Hz, 1H), 4.218 (d, J=4.0 Hz, 1H), 7.388 (d, J=10.2 Hz, 1H), 7.509-7.542 (m, 2H), 7.842-7.886 (m, 4H). 13C-NMR (CDCl3) analysis: δ 25.53, 25.81, 26.11, 28.34, 29.43, 41.10, 41.44, 78.10, 118.70, 125.19, 126.65, 126.81, 127.41, 127.69, 127.90, 129.12, 130.89, 132.88, 133.24. MS (CI+): Calcd for C19H21NO: 279.16, Found: 280.2 (M+H).
  • 23
  • [ 7498-57-9 ]
  • [ 141-78-6 ]
  • [ 51074-12-5 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: ethyl acetate In tetrahydrofuran at 60℃; Inert atmosphere;
With sodium hydride In tetrahydrofuran
Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran; mineral oil for 0.0833333h; Stage #2: ethyl acetate In tetrahydrofuran; mineral oil at 60℃;
  • 24
  • [ 1942-45-6 ]
  • [ 7498-57-9 ]
  • [ 1180490-29-2 ]
YieldReaction ConditionsOperation in experiment
85% With bis(1,5-cyclooctadiene)nickel(0); dimethylaluminum chloride; 2-dicyclohexylphosphino-2',4',6'-trimethylbiphenyl In hexane; toluene at 35℃; for 96h; Inert atmosphere; stereoselective reaction;
85% With bis(1,5-cyclooctadiene)nickel (0); dimethylaluminum chloride; 2-dicyclohexylphosphino-2',4',6'-trimethylbiphenyl In hexane; tetradecane; toluene at 35℃; for 96h; Inert atmosphere; regioselective reaction;
  • 25
  • [ 928664-98-6 ]
  • [ 580-13-2 ]
  • [ 7498-57-9 ]
  • [ 36660-46-5 ]
  • 26
  • [ 928664-98-6 ]
  • [ 580-13-2 ]
  • [ 7498-57-9 ]
  • [ 36660-46-5 ]
  • [ 581-96-4 ]
  • 27
  • [ 928664-98-6 ]
  • [ 91-58-7 ]
  • [ 7498-57-9 ]
  • 28
  • [ 928664-98-6 ]
  • [ 612-55-5 ]
  • [ 7498-57-9 ]
  • 29
  • [ 928664-98-6 ]
  • [ 3857-83-8 ]
  • [ 7498-57-9 ]
  • 30
  • [ 580-13-2 ]
  • [ 1071-36-9 ]
  • [ 7498-57-9 ]
  • 31
  • [ 91-58-7 ]
  • [ 1071-36-9 ]
  • [ 7498-57-9 ]
  • 32
  • [ 67843-74-7 ]
  • [ 7498-57-9 ]
  • [ 104-15-4 ]
  • [ 1004551-75-0 ]
YieldReaction ConditionsOperation in experiment
55% Stage #1: (S)-epichlorohydrin; 2-naphthaleneacetonitrile With sodium hexamethyldisilazane In tetrahydrofuran at -25 - -14℃; for 2.25h; Stage #2: With dimethylsulfide borane complex In tetrahydrofuran at -5 - 60℃; Stage #3: toluene-4-sulfonic acid In Isopropyl acetate at 50℃; I.1 Step 1: Synthesis of [(1S,2R)-2-(aminomethyl)-2-(2-naphthyl)cyclopropyl]methan-1-ol, p-toluenesulfonic acid salt 500g (2.99 mol, 1.0 eq) of 2-naphthylacetonitrile was charged to a 12 L 3- neck round bottom flask equipped with overhead stirrer, addition funnel, thermocouple, nitrogen inlet, cooling bath and drying tube. 3.0 L of tetrahydrofuran was added and stirred at room temperature to dissolve all solids. 360 g (3.89 mol, 1.30 eq) (S)-(+)-epichlorohydrin was added and then the solution was cooled to an internal temperature of - 25 °C. 3.0 L of a 2 molar solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (6.00 mol, 2.0 eq) was added to the reaction mixture via addition funnel at a rate such that the internal temperature of the reaction mixture is maintained at less than -15 °C. After completion of the addition, the mixture was stirred at between -20 °C and -14 °C for 2 hours 15 minutes. Borane- dimethylsulfide complex (750 mL of a 10.0 molar solution, 7.5 mol, 2.5 eq) was then slowly added to the reaction mixture at a rate such that the internal temperature was maintained at less than -5 °C. Upon completion of the borane-dimethylsulfide addition the reaction mixture was heated to an internal temperature of 60 °C and stirred overnight at this temperature. Additional borane-dimethylsulfide complex (75 mL, 0.75 mol, 0.25 eq) was then added and the reaction mixture stirred at 60 °C for 1 hour 45 minutes. The reaction mixture was cooled to room temperature and then quenched by slow addition into pre-cooled (3 °C) 2 molar aqueous hydrochloric acid (5.76 L, 11.5 mol, 3.8 eq) at a rate such that the temperature of the quench solution was maintained at less than 22 °C. The two phase mixture was then heated at an internal temperature of 50 °C for 1 hour followed by cooling to RT. Isopropyl acetate (2.0 L) and water (2.5 L) were added, the mixture agitated, and then the layers were allowed to settle. The upper organic layer was discarded. Aqueous ammonia (750 mL) was added to the aqueous layer which was then extracted with isopropylacetate (2.5 L). The aqueous layer was extracted with isopropylacetate (2.5 L) a second time. The organic extracts were combined and then sequentially washed with a 5% solution of sodium dibasic phosphate in water (2.0 L) followed by saturated brine (2.0 L). The organic layer was then concentrated to a total volume of 5.0 L and then heated to 50 °C. para-Toluene sulfonic acid monohydrate (541 g, 2.84 mol) was then added in portions. During the addition white solids precipitated and a mild exotherm was observed. Upon completion of the addition the mixture was allowed to cool to RT and the solids collected by filtration. The filtercake was washed twice with isopropylacetate, 1.0 L each wash. The filtercake was then dried to a constant weight to give 664.3 g (55% yield) of the desired product as a white solid.
  • 33
  • [ 7498-57-9 ]
  • [ 79099-07-3 ]
  • [ 1447417-89-1 ]
YieldReaction ConditionsOperation in experiment
55% With sodium methylate In methanol for 2h; Reflux; 5.1.2 tert-Butyl 4-[cyano(naphthalen-2-yl)methylidene]piperidine-1-carboxylate (16b) General procedure: A mixture of (3,4-dichlorophenyl)acetonitrile 14a (20.0g, 108mmol), tert-butyl 4-oxopiperidine-1-carboxylate 15 (21.5g, 108mmol) and 28% sodium methoxide methanol solution (23.0g, 119mmol) in MeOH (250mL) was stirred at reflux for 2h. After cooling to room temperature, MeOH was removed in vacuo, and the residue was extracted with EtOAc, washed with water and brine. The organic phase was dried over MgSO4, concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 5-50% EtOAc in hexane) to give 16a as a pale yellow oil (26.6g, 67%). 1H NMR (300MHz, CDCl3) δ 1.48 (9H, s), 2.41 (2H, t, J=5.7Hz), 2.76 (2H, t, J=5.7Hz), 3.43 (2H, t, J=5.7Hz), 3.61 (2H, t, J=5.7Hz), 7.11 (1H, dd, J=8.2, 2.1Hz), 7.38 (1H, d, J=2.1Hz), 7.48 (1H, d, J=8.2Hz). MS m/z: 311 [M+H-tBu]+. The following compounds 16b-e were prepared in a similar manner to that of 16a.
  • 34
  • [ 110-52-1 ]
  • [ 7498-57-9 ]
  • 1-(naphthalen-2-yl)cyclopentane-1-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran; mineral oil at 0 - 24℃; for 1h; Inert atmosphere; Stage #2: 1,4-dibromo-butane In tetrahydrofuran; mineral oil at 0 - 24℃; for 21h; Inert atmosphere; 2.1.3. Synthesis of 1-(naphthalen-2-yl)cyclopentane-1-carbonitrile (1h) To a suspension of sodium hydride (60% dispersion in mineral oil; 1.00 g, 25.0 mmol) in THF (10 mL) was added a solution of 2-(naphthalen-2-yl)acetonitrile (1.69 g, 10.1 mmol) inTHF (10 mL) at 0 °C. The reaction mixture was stirred for 1 h at 24 °C. To the resulting mixture was added 1,4-dibromobutane (1.4 mL, 11.7 mmol) at 0 °C. The mixture was allowed to warm up to 24 °C and stirred for 21 h. The reaction mixture was quenched withwater at 0 °C. The organic materials were extracted thrice with diethyl ether. The combined extracts were washed with brine and dried over MgSO4. The solvent was removed in vacuoand the resulting crude mixture was purified by flash column chromatography (silica gel, hexane:ethyl acetate = 49:1) to give 1h (1.83 g, 8.19 mmol) in 82% yield as white solid.
  • 35
  • [ 7498-57-9 ]
  • [ 32085-88-4 ]
  • 3-(3,5-difluorophenyl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
  • 3-(3,5-difluorophenyl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 3,5-difluorobenzaldehyde In tetrahydrofuran for 0.333333h; Inert atmosphere; 37; 141 Example 37 - Synthesis of Compound ID No. 37 f(l£25yi-(3,5-difluorophenyl)-3- (methylamino)-2-(naphthalen-2-yl)propan- 1 -ol 3-(3,5-difluorophenyl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile: To a solution of 2-naphthylacetonitrile (2 g, 11.96 mmol) in 170 mL of dry THF placed in an oven-dried round bottom flask containing a stir bar was added diisopropylamine (2 mL, 14.35 mmol) under nitrogen. The mixture was stirred and cooled to -78°C for 20 minutes. 2.5M Butyllithium (5.74 mL, 14.35 mmol) was then added slowly via a syringe. After 30 minutes, 3,5-difluoro-benzaldehyde (2 mL, 14.35 mmol) was added drop-wise via syringe, and the reaction was monitored by TLC for completion. After 20 minutes, the reaction was quenched quickly with 10 mL 2:1 THF/acetic acid (added all at once). Cold bath was removed, and the reaction was allowed to reach room temperature. Water was added, and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with water and brine, dried over MgS04, and concentrated under reduced pressure. The two diastereomeric adducts in the residue were effectively separated by silica gel flash chromatography (elution with 15% to 40% EtOAc in hexanes). Tentative stereochemistry for each diastereomer was assigned on the basis of polarity (TLC mobility) and the J- values of the proton on the benzylic position in the 1H NMR. anti- isomer: (1.2 g, 32%) XH NMR (CDCh) 5, 7.89-7.79 (m, 4 H), 7.60-7.49 (m, 2 H), 7.31 (dd, 1 H, J= 8.5, 1.70 Hz), 6.95-6.84 (m, 2 H), 6.81-6.71 (m, 1 H), 5.06 (d, 1 H, J = 4.9 Hz), 4.22 (d, 1 H, J = 5.0 Hz), syn- isomer (2.5 g, 67.6%). (1.7 g, 47%). 1H NMR (CZX) δ 7.92-7.79 (m, 3 H), 7.75 (s, 1 H), 7.59-7.50 (m, 2 H), 7.32 (dd, 1 H, J= 8.48, 1.7 Hz), 6.92-6.73 (m, 3 H), 5.08 (d, 1 H, J= 6.6 Hz), 4.24 (dd, 1 H, J= 6.8 Hz).
  • 36
  • [ 7498-57-9 ]
  • [ 529-20-4 ]
  • 2-(naphthalen-2-yl)-3-(o-tolyl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With sodium ethanolate In ethanol for 0.25h; 39a Example 39a - Synthesis of Compound No. 39a (2-fnaphthalen-2-yl)-3-(o- tolyPacrylonitrile) To a stirred solution of 2-napthtlyacetonitrile (1.72 g, 10.3 mmol) in absolute ethanol (15 mL) was added o-tolylbenzaldehyde (1.2 mL, 10.3 mmol). A solution of sodium ethoxide (68 mg, 1.03 mmol) in absolute ethanol (2 mL) was added. Within 15 minutes, a solid was formed, and to this suspension was added 15 mL of hot THF. The solution was then concentrated, and the solid was purified via silica gel flash chromatography (50% EtOAc in hexanes) to give 2.05 g (7.5 mmol, 74%) of a white amorphous solid. 1H NMR (400 MHz, CDC13) δ 8.19 (d, J= 1.8 Hz, 1H), 8.03 - 7.84 (m, 5H), 7.78 (dd, J= 8.7, 2.0 Hz, 1H), 7.63 - 7.49 (m, 2H), 7.43 - 7.25 (m, 3H), 2.44 (s, 3H).
  • 37
  • [ 98-03-3 ]
  • [ 7498-57-9 ]
  • 3-hydroxy-2-(naphthalen-2-yl)-3-(thiophen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: thiophene-2-carbaldehyde In tetrahydrofuran for 0.166667h; Inert atmosphere; 40; 47 Example 40 - Synthesis of Compound ID No. 40 (fi?,SVN-methyl-2-(naphthalen-2- yl)-3 -(thiophen-2-vOpropan- 1 -amine) ai/'-3-hydroxy-2-(naphthalen-2-yl)-3-(thiophen-2-yl)propanenitrile: A solution of 2-naphthylacetonitrile (6.0 g, 35.9 mmol) in 150 mL of dry THF was placed in an oven-dried round bottom flask with stirred under nitrogen.Diisopropylamine (6.04 mL, 43.1 mmol) was added, and the mixture was stirred and cooled to -78°C for 20 minutes. 2.5 M butyllithium (17.22 mL, 43.1 mmol) was then added slowly with a syringe. After 30 minutes of stirring at -78°C, thiophene-2- carboxaldehyde (3.96 mL, 43.1 mmol) was added drop-wise via syringe. After 10 minutes, the reaction was quenched quickly with 25 mL 2: 1 THF/acetic acid. Cold bath was removed, and the reaction was allowed to reach room temperature slowly. Water was added, and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with water and brine, dried over MgS04, and concentrated using a rotary evaporator. The anti- product in the residue was purified by silica gel flash chromatography (eluting with 15% to 20% EtOAc in hexanes) to afford the product as a light yellow solid (8.1 g, 81 %). 1H NMR (CDCl3) δ 7.89-7.75 (m, 4 H), 7.56-7.47 (m, 2 H), 7.35-7.26 (m, 2 H), 6.94-6.86 (m, 2 H), 5.34 (d, 1 H, J= 6.0 Hz), 4.31 (d, 1 H, J= 5.7 Hz ). MS m/z (ESI) 302.20 (MNa+).
  • 38
  • [ 13679-70-4 ]
  • [ 7498-57-9 ]
  • 3-hydroxy-3-(5-methylthiophen-2-yl)-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
31.6% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 5-methylthiophene-2-carboxaldehyde In tetrahydrofuran for 0.166667h; 44 Example 44 - Synthesis of Compound ID No. 44 (CS -N-methyl-3-(5-methylthiophen- 2-yl)-2-fnaphthalen-2-yl)propan- 1 -amine) 4i/-3-hydroxy-3-(5-methylthiophen-2-yl)-2-(naphthalen-2-yl)propanenitrile: Diisopropylamine (4.02 mL, 28.7 mmol) was added to a solution of 2- naphthylacetonitrile (4 g, 23.92 mmol) in 150 mL of dry THF under nitrogen. The mixture was stirred and cooled to -78 °C for 20 minutes before adding 2.5M n- butyllithium (1 1.48 mL, 28.7 mmol) in a dropwise fashion via a syringe. After 30 minutes of stirring at -78 °C, 5-methylthiophene-2-carboxaldehyde (3.07 mL, 28.7 mmol) was added slowly via a cannula. After 10 minutes, the reaction was quickly quenched with 25 mL 2: 1 THF/acetic acid. Cold bath was removed and the reaction was allowed to reach r.t slowly. Water was added and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with water and brine, dried over MgS04, and concentrated using a rotary evaporator. The resulting residue was dissolved in 5 mL of DCM. Hexane was slowly added till the solution turned turbid. This product was allowed to crystallize overnight at room temperature. Light brown crystals of the n/z'-adduct were filtered and washed with hexane and dried (2.5 g, 31.6%). 1H NMR (CDCl3) δ 7.86-7.79 (m, 4 H), 7.56-7.46 (m, 2 H), 7.34 (dd, 1 H, J= 8.7, 1.5 Hz), 6.68 (d, 1 H, J= 3.6 Hz), 6.55 (m, 1 H), 5.27 (dd, 1 H, J= 5.4, 5.4 Hz), 4.29 (d, 1 H, J= 6.0 Hz), 2.55 (d, 1 H, J= 5.4 Hz), 2.48 (s, 3 H). MS m/z (ESI) 316.08 (MNa+). The relative anti configuration of this compound was confirmed after borane reduction.
  • 39
  • [ 72990-37-5 ]
  • [ 7498-57-9 ]
  • 3-(3-chloropyridin-4-yl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
  • 3-(3-chloropyridin-4-yl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; These compounds were made in a standard LDA-mediated reaction of 2-naphthylacetonitrile and 3-chloro-4-pyridine carboxaldehyde at -78 C in THF. The syn aldol was isolated and identified in the customary way: 1H NMR (CDCI3) delta8.57 (s, 1 H), 8.30 (d, 1 H, J= 5.1 Hz), 7.83-7.76 (m, 1 H), 7.75-7.68 (m, 2 H), 7.61(bs, 1 H), 7.53-7.49 (m, 2 H), 7.12 (dd, 1 H, J= 8.4, 1.6 Hz), 7.08 (d, 1 H, J= 4.8Hz), 5.86 (t, 1 H, J = 4.5 Hz), 4.46 (d, 1 H, J= 4.5 Hz), 2.86 (d, 1 H, J= 4.5 Hz).
  • 40
  • [ 500-22-1 ]
  • [ 7498-57-9 ]
  • C18H12N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With sodium ethanolate In ethanol 48 Example 48 - Synthesis of Compound ID No. 48 ((>SyN-methyl-2-(naphthalen-2-yl)-3 -(pyridin-3 -vDpropan- 1 -amine) The aldol condensation using sodium ethoxide, ethanol, 3-pyridine- carboxaldehyde (590 mg, 5.05 mmol) and 2-naphthylacetonitirle (836 mg, 5.0 mmol) was performed in the usual way to give 1.21 g (4.72 mmol, 95%) of a yellow solid. The conjugate reduction was performed in the usual way with a portion of the above material (554 mg, 2.16 mmol) to give 179 mg (0.68 mmol, 32%>) of a crude yellow oil.
  • 41
  • [ 7498-57-9 ]
  • [ 5896-17-3 ]
  • C26H19NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With sodium ethanolate In ethanol 52a; 133a Example 52a - Synthesis of Compound No. 52a (fert-butyl (3-(2-(benzyloxy)phenyl)-2-(naphthalen-2-yl propyl carbamate The aldol condensation using sodium ethoxide, ethanol, 2- benzyloxybenzaldehyde (1.07 g, 5.05 mmol) and 2-naphthylacetonitiiie (836 mg, 5.0 mmol) was performed in the usual way to give 1.73 g (4.8 mmol, 96%) of a yellow solid.
  • 42
  • [ 1121-60-4 ]
  • [ 7498-57-9 ]
  • 3-hydroxy-2-(naphthalen-2-yl)-3-(pyridin-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
25.2% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: pyridine-2-carbaldehyde In tetrahydrofuran for 0.166667h; Inert atmosphere; 72 Example 72 - Synthesis of Compound ID No. 72 ((\R,2S and 1S.2R V3-(methylamino -2-(naphthalen-2-yl -l-(pyridin-2-yl propan-l-ol iy-3-Hydroxy-2-(naphthalen-2-yl)-3-(pyridin-2-yl)piOpanenitrile: A solution of 2-naphthylacetonitrile (5 g, 29.9 mmol) in 200 mL of dry THF was placed in an oven-dried round bottom flask with under nitrogen. Diisopropylamine (5.03 mL, 35.9 mmol) was added, and the reaction mixture was stirred and cooled to -78°C for 20 minutes. 2.5M butyllithium (14.35 mL, 35.9 mmol) was then added slowly with a syringe. After 30 minutes of stirring at -78°C, pyridine 2-carboxaldehyde (3.56 mL, 35.9 mmol) was added drop-wise via syringe. After 10 minutes, the reaction was quenched quickly with 25 mL 2: 1 THF/acetic acid. The cold bath was removed, and the reaction was allowed to reach room temperature. Water was added, and the aqueous layer was extracted with EtOAc (3 x 25 mL). The combined organic layers were sequentially washed with water and brine, then dried over MgS04, and concentrated using a rotary evaporator. The residue was dissolved in DCM, and hexane was slowly added until a turbid solution resulted. The turbid solution was allowed to stand for 15 minutes. The major syn-isomer that separated as off-white crystals was isolated by filtration (1.033 g, 7.53 mmol, 25.2%). 1H NMR (DMSO. 6) δ 8.51 (d, 1 H, J= 4.3 Hz), 7.91-7.77 (m, 3 H), 7.74-7.65 (m, 2 H), 7.55-7.46 (m, 2 H), 7.34-7.22 (m, 3 H), 6.37 (d, 1 H, J= 5.5 Hz), 5.19 (t, 1 H, J= 5.5 Hz ), 4.86 (d, 1 H, J= 5.5 Hz). MS m/z (ESI) 275.30 (MH+).
  • 43
  • [ 7498-57-9 ]
  • [ 113118-83-5 ]
  • 3-hydroxy-3-(5-methoxypyridin-3-yl)-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% A 250 mL round bottom flask equipped with a magnetic stirring bar, nitrogen inlet, and septum was charged with THF (100 mL) and butyllithium (7.29 mL, 18.23 mmol). After cooling to -78C, 2-(naphthalen-2-yl)acetonitrile (3.05 g, 18.23 mmol) was added, and after 60 minutes, <strong>[113118-83-5]5-methoxynicotinaldehyde</strong> (2.5 g, 18.23 mmol) was added via syringe. After stirring at (-78C) for 3 hours, the reaction was quenched by the addition of acetic acid (2.1 mL) while stirring at -70C. The aqueous layer was extracted with Et20 (2 x 250 mL), and the combined organic extracts were washed with brine (250 mL) and dried (MgSC^). The material was concentrated in vacuo to give a crude aldol (6 g). ISCO purification on silica gel eluting with 0-100% of ethyl acetate in hexane afforded the product as an antv.syn mixture (4 g, 72%). 1H NMR (500 MHz, CDCk) delta 2.80 (d, J=3.7 Hz, 1 H), 3.78 (s, 3 H), 4.24 (d, J=5.2 Hz, 1 H), 5.12 (d, J=3.4 Hz, 1 H), 7.18 - 7.38 (m, 4 H), 7.47 - 7.61 (m, 2 H), 7.73 - 7.93 (m, 5 H), 8.04 (d, J=1.5 Hz, 1 H), 8.23 (d, J=2.7 Hz, 1 H).
  • 44
  • [ 7498-57-9 ]
  • [ 113118-83-5 ]
  • 3-hydroxy-3-(5-methoxypyridin-3-yl)-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
  • 3-hydroxy-3-(5-methoxypyridin-3-yl)-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
A 250 mL round bottom flask equipped with a magnetic stirring bar, nitrogen inlet, and septum was charged with THF (100 mL) and butyllithium (7.29 mL, 18.23 mmol). After cooling to -78C, 2-(naphthalen-2-yl) acetonitrile (3.05 g, 18.23 mmol) was added. After 60 minutes, <strong>[113118-83-5]5-methoxynicotinaldehyde</strong> (2.5 g, 18.23 mmol) was added via syringe, and the reaction mixture was stirred at -78C for 3 hours. The reaction was quenched by the addition of acetic acid (2.1 mL) while stirring at -70C. The aqueous layer was extracted with ether (2 x 250 mL), and the combined organic extracts were washed with brine (250 mL), dried over MgS04, and concentrated in vacuo to give the crude aldol (6.0 g). ISCO purification on silica gel eluting with 0- 100% ethyl acetate in hexane afforded the product as antv.syn mixture (4.0 g).Recrystallization from THF (10 mL) and hexane (25 mL) at 0C overnight afforded anti mixture as a solid (1.4 g) and anti/syn mixture (1 : 1.5) as an oil (2.5 g). Second recrystallization of the anti mixture from THF/hexane afforded the pure anti diastereomer (1.2 g). 1H NMR (CDCl3) delta 8.23 (d, 1 H, J = 2.7 Hz), 8.04 (d, 1 H, J = 1.5 Hz), 7.93 - 7.73 (m, 5 H), 7.61 - 7.47 (m, 2 H), 7.38 - 7.18 (m, 4 H), 5.12 (d, 1 H, J = 3.4 Hz), 4.24 (d, 1 H, J = 5.2 Hz), 3.78 (s, 3 H), 2.80 (d, 1 H, J = 3.7 Hz). MS m/z (ESI) 305.13 (MH+).
  • 45
  • [ 7498-57-9 ]
  • [ 1550-35-2 ]
  • 3-(2,4-difluorophenyl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
32.4% Stage #1: 2-naphthaleneacetonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2,4-difluorobenzaldehyde In tetrahydrofuran; hexane Inert atmosphere; 107 Example 107 - Synthesis of Compound ID No. 107 (Yli 5V3-amino-l-f2,4- difluorophenyl)-2-fnaphthalen-2-yl)propan- 1 -ol) syn-3-(2,4-difiuorophenyl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile: 2- Naphthylacetonitrile (2.5 g, 14.95 mmol) was taken in an oven-dried round bottom flask containing a stir bar and 170 mL of dry THF was added under nitrogen.Diisopropylamine (2.5 mL, 17.94 mmol) was added and the mixture was stirred and cooled to -78°C for 20 minutes. Butyllithium (2.5 M in hexane, 7.18 mL, 17.94 mmol) was then added slowly via syringe. After 30 minutes, 2,4-difluorobenzaldehyde (1.964 mL, 17.94 mmol) was added dropwise via syringe slowly. After 10 min, the reaction was quenched with quick addition of a mixture of 10 mL 2:1 THF /acetic acid (add all at once). Cold bath was removed, and the reaction was warmed to room temperature. Water was added, and the layers were separated. The aqueous layer was extracted with EtOAc (3 x 100 mL), and the combined organic layers were washed with water and brine, and dried over MgS04. The combined organic layers were concentrated using a rotary evaporator. The residue was dissolved in 25 mL of DCM and 80 mL of hexane. A turbid solution resulted that was kept at 4 °C for 2 hours. After filtration, the product from first crystallization was redissolved in 30 mL of DCM, and 150 ml of hexane was slowly added. The resulting white crystals were filtered and dried under vacuum (yield 0.5 g, 4.85 mmol, 32.4%). 1H NMR (CDC13) δ 7.88-7.76 (m, 3 H), 7.70 (s, 1 H), 7.57-7.48 (m, 2 H), 7.40-7.26 (m, 2 H), 6.89-6.72 (m, 2 H), 5.47 (t, 1 H, J = 4.9 Hz), 4.35 (d, 1 H, J = 6.0 Hz), 2.42 (d, 1 H, J = 6.0 Hz). MS m z (ESI) 309.45 (MH+).
  • 46
  • [ 850832-54-1 ]
  • potassium 2-naphthyltrifluoroborate [ No CAS ]
  • [ 7498-57-9 ]
  • 47
  • [ 7498-57-9 ]
  • [ 92874-17-4 ]
  • 2-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-(naphthalen-2-yl)acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: 4-bromo-N-butylnaphthalimide In tetrahydrofuran Typical Procedures General procedure: Anhydrous THF (25 mL) solution of 2a (0.40 g, 3.42 mmol) was stirred for 1 h at r.t., then N-butyl-4-bromo-1,8-naphthalimide(1, 1.00 g, 3.02 mmol) was added. After completion, the reaction mixture was quenched with HCl (15%) until pH 2-3. The organic fraction was extracted with EtOAc (3 × 20 mL), dried over anhydrous Na2SO4, and filtered. Volatile fractions were removed under reduced pressure, and the residual material was purified by flash column chromatography on silica gel (PE-EtOAc, 25:1) to provide 3a as a pink solid 0.80 g (72% yield).
  • 48
  • [ 7498-57-9 ]
  • [ 100-51-6 ]
  • 2-(naphthalen-2-yl)-3-phenylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With chloro(1,5-cyclooctadiene)rhodium(I) dimer; triphenylphosphine; potassium hydroxide In tert-Amyl alcohol at 130℃; for 2h; Microwave irradiation;
88% With chloro(1,5-cyclooctadiene)rhodium(I) dimer; triphenylphosphine; potassium hydroxide at 130℃; for 2h; Microwave irradiation; Green chemistry; 24 Example 24: 3-Phenyl-2- (2-naphthyl) propanamide 2-Naphthylacetonitrile (167 mg, 1 mmol),Benzyl alcohol (119 mg, 1.1 mmol), [Rh (cod) Cl] 2 (4.9 mg, 0.01 mmol, 1 mol%),Triphenylphosphine (26 mg, 0.1 mmol, 10 mol%),Potassium hydroxide (22 mg, 0.4 mmol, 40 mol%) were sequentially added to a 10 ml microwave reaction tube.The mixture was reacted at 130 ° C for 2 hours and then cooled to room temperature. The solvent was removed by rotary evaporation and then the title compound was obtained by column chromatography (developing solvent: ethyl acetate / petroleum ether) in 88% yield.
77% With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; 1,10-Phenanthroline; potassium <i>tert</i>-butylate at 140℃; for 6h; Inert atmosphere; 34 Example 34: Synthesis of 2-(2-naphthyl)-3-phenylpropionamide benzyl alcohol (0.216g, 2.0mmol) and 2-naphthaleneacetonitrile (0.167g, 1.0mmol) were dissolved in 1.0 mL of tert-amyl alcohol and combined with 7.9mg (1.0mol%) of [Cp*IrCl2]2, 3.6mg (2.0 mol%) 1,10-phenanthroline and 22.4 mg (20 mol%) potassium tert-butoxide were added to the pressure tube together, and after nitrogen replacement, the reaction was carried out at 140°C for 6 hours. The obtained reaction solution was cooled to room temperature, extracted with water and ethyl acetate, the organic phase was separated, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by rapid preparative liquid chromatography (the volume ratio of ethyl acetate: petroleum ether was 30:100). The eluent containing the target compound was collected, and then evaporated under reduced pressure to obtain 0.212 g of the compound represented by formula 3, with a yield of 77% and a purity of the liquid phase of 99%.
77% With 2,2':6,2''-terpyridine; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; potassium <i>tert</i>-butylate In tert-Amyl alcohol at 150℃; for 5h; Inert atmosphere; chemoselective reaction;

  • 49
  • [ 7498-57-9 ]
  • [ 109-64-8 ]
  • [ 161190-37-0 ]
YieldReaction ConditionsOperation in experiment
53% With sodium hydride In tetrahydrofuran; dimethyl sulfoxide; mineral oil at 0 - 24℃; for 21h; Inert atmosphere; 2.1.2. Synthesis of 1-(naphthalen-2-yl)cyclobutane-1-carbonitrile (1g) A solution of 2-(naphthalen-2-yl)acetonitrile (1.67 g, 10.0 mmol) and 1,3-dibromopropane (1.1 mL, 10.8 mmol) in THF (20 mL) was added dropwise to a mixture of sodium hydride (60% dispersion in mineral oil; 1.00 g, 25.0 mmol) in DMSO (20 mL) at 0 °C. The mixture was allowed to warm up to 24 °C and stirred for 21 h. The reaction mixture was quenched with water at 0 °C. The organic materials were extracted thrice with diethyl ether. The combined extracts were washed with brine and dried over MgSO4. The solvent was removed in vacuo and the resulting crude mixture was purified by flash column chromatography (silica gel, hexane:ethyl acetate = 49:1) to give 1g (1.10 g, 5.29 mmol) in 53% yield as white solid
With potassium hydroxide In dimethyl sulfoxide at 0 - 20℃;
With potassium hydroxide In dimethyl sulfoxide at 20℃; for 12h;
  • 50
  • [ 30082-24-7 ]
  • [ 7498-57-9 ]
  • 2-(1-methyl-1H-indol-3-yl)naphtho[1,2-b]thiophene-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% Stage #1: 2-naphthaleneacetonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Stage #2: methyl (1-N-methyl-3-indolyl)-3-carbodithioate In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1h; Stage #3: With tetrabutylammomium bromide; copper diacetate; palladium diacetate In N,N-dimethyl-formamide; mineral oil at 90℃;
80% Stage #1: 2-naphthaleneacetonitrile With potassium <i>tert</i>-butylate In 1,4-dioxane at 0℃; for 0.166667h; Stage #2: methyl (1-N-methyl-3-indolyl)-3-carbodithioate In 1,4-dioxane at 0 - 20℃; for 1h; Stage #3: With iodine In 1,4-dioxane at 90℃; Synthesis of Benzo[b]thiophenes 3 from arylacetonitriles 1 and (het)aryl dithioesters 2 General procedure: To a stirring suspension of KOtBu (2.0 mmol) in 1,4-dioxane (5 mL) at 0°C, corresponding (het)arylacetonitrile (1a-f, 10a-c) (1.0 mmol) in 1,4-dioxane (2 mL) was added dropwise. After further stirring for 10 minutes, a solution of respective Dithioester (2a-i) (1.0 mmol) in 1,4-dioxane (2 mL) was added to the reaction mixture at 0°C, followed by further stirring for 1 h at ambient temperature (monitored by TLC). Iodine (506 mg, 2.0 mmol) was added and the reaction mixture was heated at 90°C with continuous stirring (monitored by TLC). It was then diluted with 10% aq. Na2S2O3 solution (50 mL) and extracted with EtOAc (3x25 mL), and the combined organic layer was washed with water (3x25 mL) and brine (1x25 mL), dried (anhyd. Na2SO4), and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography using EtOAc/hexane as eluent.
  • 51
  • [ 7498-57-9 ]
  • [ 141-43-5 ]
  • 2-naphthalen-2-ylmethyl-4,5-dihydrooxazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With sulfur In neat (no solvent) at 50 - 80℃; Green chemistry; General procedure for the preparation of 2-oxazolinesfrom nitriles General procedure: An equimolar mixture of 2-aminoethanol (1.0 mmol) and sulfur(1.0 mmol) was heated under solvent-free condition at 50°C. Nitrile (1.0 mmol) was then added to reaction mixture and refluxed at 80°C. The progress of the reaction was monitored through TLC (n-hexane: EtOAc, 8:2). After completion of the reaction, excess of water was added, and the product was filtered (for solid). Further chromatographic purification afforded pure product. All the compounds were characterizedby infrared (IR) and 1H NMR and 13C NMR spectroscopic data, as well as by comparison with data of reported compounds.
  • 52
  • [ 7498-57-9 ]
  • [ 766-47-2 ]
  • (Z)-2-(naphthalen-2-yl)-4-(o-tolyl)but-2-enenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With potassium <i>tert</i>-butylate In dimethyl sulfoxide; <i>tert</i>-butyl alcohol at 80℃; for 12h; Inert atmosphere; stereoselective reaction; 17 In the reaction flask was added 0.3 mmol of o-methyl phenylacetylene, 0.3 mM 2-naphthylacetonitrile, 0.3 mmol of potassium tert-butoxide, 0.3 mmol of tert-butyl alcohol, 1 ml of dimethylsulfoxide, at 80 after stirring under nitrogen protection ° C 12 hours to stop the heating and stirring, cooled to room temperature.The reaction was washed with 15mL water, then extracted three times with ethyl acetate (each with I OmL), combined organic layers were dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and then purified by column chromatography to give the desired product, column chromatography eluent used was a volume ratio of 100: 1 n-hexane and ethyl acetate mixed solvent, a yield of 76%.
76% With potassium <i>tert</i>-butylate; <i>tert</i>-butyl alcohol In dimethyl sulfoxide at 80℃; for 12h; Inert atmosphere; stereoselective reaction;
  • 53
  • [ 7498-57-9 ]
  • [ 2243-82-5 ]
YieldReaction ConditionsOperation in experiment
90% With oxygen; ammonium chloride; copper(II) oxide; In 1,4-dioxane; N,N-dimethyl-formamide; at 80℃;Sealed tube; The reaction vessel was charged with 10 molpercent of CuO, the reaction tube was evacuated and filled with oxygen, and 0.2 mmol of 2-naphthaleneacetonitrile, 0.4 mmol of ammonium chloride, 1 ml of N, N-dimethylformamide and 1 ml of 1, 4-dioxane, the reaction vessel was sealed, reacted at 80 ° C,After the reaction was completed, it was washed with water, extracted with chloroform, dried and concentrated by evaporation under reduced pressure to remove the solvent. The crude product was separated by column chromatography to give the desired product in a yield of 90percent.
  • 54
  • [ 7498-57-9 ]
  • [ 23612-57-9 ]
  • [ 100-51-6 ]
  • N-benzyl-3-(naphthalen-2-yl)-1,8-naphthyridin-2-amine [ No CAS ]
  • 55
  • [ 7498-57-9 ]
  • [ 86-52-2 ]
  • [ 855628-36-3 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: 2-naphthaleneacetonitrile; 1-Chloromethylnaphthalene With palladium diacetate; sodium hydride; Tri(p-tolyl)phosphine In 1,4-dioxane at 45℃; for 12h; Inert atmosphere; Stage #2: With oxygen In 1,4-dioxane for 10h; 4 Example 4: Synthesis of 2- (4'-methyl-1'-naphthyl) -naphthylmethanone In a 25 mL reactor, sodium hydride (0.048 g, 1.2 mmol), palladium acetate (0.003 g, 0.015 mmol) andTris (p-tolyl) phosphine (0.009 g, 0.030 mmol),After the nitrogen was replaced three times, 5 mL of anhydrous 1,4-dioxane was added,2-Naphthylacetonitrile (0.100 g, 0.6 mmol) and 1-chloromethylnaphthalene (0.053 g, 0.3 mmol) were added with stirring,After stirring at 45 ° C for 12 h,Oxygen was added to the reaction solution and stirring was continued for 10 h,(Silica gel, 200-300 mesh; developing solvent, petroleum ether: ethyl acetate = 100: 1) to give 0.066 g of 2- (4'-methyl-1'-naphthyl) -naphthylmethanone, Yield 74%.
74% Stage #1: 2-naphthaleneacetonitrile; 1-Chloromethylnaphthalene With palladium diacetate; sodium hydride; tert-butyldiphenylphosphine In 1,4-dioxane; mineral oil at 30℃; for 12h; Inert atmosphere; Stage #2: In 1,4-dioxane; mineral oil at 30℃; for 12h; Inert atmosphere; regioselective reaction;
  • 56
  • [ 589-18-4 ]
  • [ 7498-57-9 ]
  • 2-(naphthalen-2-yl)-3-(p-tolyl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With [(bis(2-dicyclohexylphosphinoethyl)amine)Fe(CO)Br2]; sodium triethylborohydride; sodium hydroxide In toluene at 130℃; for 6h; Glovebox; Sealed tube; Inert atmosphere; Flow reactor; High pressure;
82% With C32H25Cl2N6O2Rh2(1+)*Cl(1-); sodium hydroxide In toluene at 110℃; for 24h; Sealed tube; Inert atmosphere; chemoselective reaction;
76% With C18H13BrMnN3O3S; potassium <i>tert</i>-butylate In tert-Amyl alcohol at 140℃; for 24h; Inert atmosphere;
  • 57
  • [ 7498-57-9 ]
  • [ 69922-39-0 ]
  • 2-(benzo[d][1,3]dioxol-5-yl)naphtho[1,2-b]thiophene-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: 2-naphthaleneacetonitrile With potassium <i>tert</i>-butylate In 1,4-dioxane at 0℃; for 0.166667h; Stage #2: C9H8O2S2 In 1,4-dioxane at 0 - 20℃; for 1h; Stage #3: With iodine In 1,4-dioxane at 90℃; Synthesis of Benzo[b]thiophenes 3 from arylacetonitriles 1 and (het)aryl dithioesters 2 General procedure: To a stirring suspension of KOtBu (2.0 mmol) in 1,4-dioxane (5 mL) at 0°C, corresponding (het)arylacetonitrile (1a-f, 10a-c) (1.0 mmol) in 1,4-dioxane (2 mL) was added dropwise. After further stirring for 10 minutes, a solution of respective Dithioester (2a-i) (1.0 mmol) in 1,4-dioxane (2 mL) was added to the reaction mixture at 0°C, followed by further stirring for 1 h at ambient temperature (monitored by TLC). Iodine (506 mg, 2.0 mmol) was added and the reaction mixture was heated at 90°C with continuous stirring (monitored by TLC). It was then diluted with 10% aq. Na2S2O3 solution (50 mL) and extracted with EtOAc (3x25 mL), and the combined organic layer was washed with water (3x25 mL) and brine (1x25 mL), dried (anhyd. Na2SO4), and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography using EtOAc/hexane as eluent.
  • 58
  • [ 35972-85-1 ]
  • [ 7498-57-9 ]
  • 2-(furan-2-yl)naphtho[1,2-b]thiophene-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 2-naphthaleneacetonitrile With potassium <i>tert</i>-butylate In 1,4-dioxane at 0℃; for 0.166667h; Stage #2: methyl furan-2-carbodithioate In 1,4-dioxane at 0 - 20℃; for 1h; Stage #3: With iodine In 1,4-dioxane at 90℃; Synthesis of Benzo[b]thiophenes 3 from arylacetonitriles 1 and (het)aryl dithioesters 2 General procedure: To a stirring suspension of KOtBu (2.0 mmol) in 1,4-dioxane (5 mL) at 0°C, corresponding (het)arylacetonitrile (1a-f, 10a-c) (1.0 mmol) in 1,4-dioxane (2 mL) was added dropwise. After further stirring for 10 minutes, a solution of respective Dithioester (2a-i) (1.0 mmol) in 1,4-dioxane (2 mL) was added to the reaction mixture at 0°C, followed by further stirring for 1 h at ambient temperature (monitored by TLC). Iodine (506 mg, 2.0 mmol) was added and the reaction mixture was heated at 90°C with continuous stirring (monitored by TLC). It was then diluted with 10% aq. Na2S2O3 solution (50 mL) and extracted with EtOAc (3x25 mL), and the combined organic layer was washed with water (3x25 mL) and brine (1x25 mL), dried (anhyd. Na2SO4), and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography using EtOAc/hexane as eluent.
  • 59
  • [ 7498-57-9 ]
  • [ 108-93-0 ]
  • C18H17N [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium <i>tert</i>-butylate In toluene at 135℃; for 10h; Inert atmosphere; Green chemistry;
  • 60
  • [ 7498-57-9 ]
  • diphenyl(vinyl)sulfonium trifluoromethanesulfonate [ No CAS ]
  • [ 124277-03-8 ]
YieldReaction ConditionsOperation in experiment
92% With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 21℃; for 12h; General Procedure B: for aryl / heteroaryl acetonitriles substrate’s cyclopropanation General procedure: To a 5 mL Schlenk tube were added aryl / heteroaryl acetonitriles 1 (1.0 mmol, 1.0 equiv.), vinyl diphenylsulfonium triflate (434.4 mg, 1.2 mmol, 1.2 equiv.), and DMSO (5 mL). The mixture was stirred at room temperature for 2 min and to the mixture DBU (456 mg, 3 mmol, 3.0 equiv.) was added. The mixture was stirred for 12 hours at room temperature, and then to the mixture was added saturated ammonium chloride solution (25 mL). The resulting mixture was extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with H2O (2 x 30 mL), dried with anhydrous sodium sulfate. After concentration, product 2 was purified using silica gel column chromatography using an appropriate eluent.
  • 61
  • potassium cyanide [ No CAS ]
  • [ 1592-38-7 ]
  • [ 7498-57-9 ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: 2-Naphthalenemethanol With thionyl chloride at 50℃; Inert atmosphere; Stage #2: potassium cyanide In ethanol at 50℃; for 3h; Inert atmosphere; 3 4.3 Experimental procedure and spectroscopic data for 2-naphthylacetonitrile (8) A mixture of 2-naphthylmethanol 6 (1 g, 6.3 mmol) and SOCl2 (15 mL) was stirred overnight at 50 °C. After removing the excess of SOCl2 under vacuum, 10 mL of ethanol were added and the mixture was stirred for 15 min at room temperature. Then, 6 mL of a potassium cyanide solution (6 M) were added and the mixture was stirred vigorously at 50 °C for 3 h and then poured into 50 mL of water and stirred for 30 min. The precipitate formed was recovered by filtration on fritted glass to give 0.8 g (76%) of the desired product 8 as a white solid. m.p = 82-84 °C; 1H NMR (300 MHz, CDCl3): δ (ppm): 3.91 (s, 2H, CH2); 7.38 (dd, J1 = 1.5 Hz, J2 = 8.4 Hz, 1H); 7.53-7.55 (m, 2H); 7.84-7.89 (m, 4H); 13C NMR (75 MHz, CDCl3): δ (ppm): 23.26 (CH2); 117.14 (CN); 124.90 (C-H); 125.97 (C-H); 126.25 (C-H); 126.36 (C-H); 126.79 (C-H); 127.19 (C); 127.22 (CH); 128.54 (C-H); 132.31 (C); 132.93 (C).
  • 62
  • [ 7498-57-9 ]
  • [ 459-57-4 ]
  • (Z)-3-(p-fluorophenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 1 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.White powder, 85%, m.p=143-145°C; 1H NMR (300MHz, CDCl3): δ (ppm): 7.54-7.58 (m, 2H); 7.64 (s, 1H); 7.70-7.78 (m, 3H); 7.86-7.89 (m, 1H), 7.91 (d, J=8.1Hz, 2H); 8.00 (d, J=8.4Hz, 2H); 8.21 (s, 1H, Hvinyl); 13C NMR (75MHz, CDCl3): δ (ppm): 114.02 (C); 116.96 (CN); 121.78 (CH); 125.41 (CH); 125.46 (CH); 126.34 (CH); 126.68 (CH); 126.95 (CH); 127.25 (CH); 128.11 (CH); 128.62 (CH); 128.94 (2CH); 130.45 (C); 131.12 (C); 132.71 (C); 133.17 (C); 136.61 (C); 139.46 (CH); 19F NMR (282MHz, CDCl3): δ (ppm): -109.84
  • 63
  • [ 455-19-6 ]
  • [ 7498-57-9 ]
  • (Z)-3-(p-trifluoromethylphenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 2 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 64
  • [ 7498-57-9 ]
  • [ 1571-08-0 ]
  • methyl (Z)-p-[2-cyano-2-(naphthalen-2-yl)]vinylbenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 3 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 65
  • [ 7498-57-9 ]
  • [ 123-11-5 ]
  • (Z)-3-(p-methoxyphenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 4 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 66
  • [ 7498-57-9 ]
  • [ 105-07-7 ]
  • (Z)-3-(p-cyanophenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 5 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 67
  • [ 7498-57-9 ]
  • [ 3446-89-7 ]
  • (Z)-3-(p-(methylthio)phenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 6 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 68
  • [ 7498-57-9 ]
  • [ 120-14-9 ]
  • (Z)-3-(3',4'-dimethoxyphenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With sodium methylate In methanol at 0 - 20℃; for 6.5h; Inert atmosphere; 7 General procedure for the preparation of unsaturated α,β-nitriles (9a-h) General procedure: A mixture of 1M equivalent of 2-naphthylacetonitrile (7) and 1M equivalent of aldehyde in dry methanol (30mL) was stirred at 0°C for 10min. Then, sodium methoxide (2 equiv.) was added in small portions and the mixture was stirred for 30 min at 0°C, and then for 6h at room temperature. The resulting precipitate was collected by filtration on a fritted glass, washed with water and dried.
  • 69
  • [ 64-17-5 ]
  • [ 7498-57-9 ]
  • 2-(naphthalen-2-yl)butanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With C18H13BrMnN3O3S; potassium <i>tert</i>-butylate In tert-Amyl alcohol at 140℃; for 24h; Inert atmosphere;
60% With [(bis(2-dicyclohexylphosphinoethyl)amine)Fe(CO)Br2]; sodium triethylborohydride; sodium hydroxide In toluene at 130℃; for 24h; Glovebox; Sealed tube; Inert atmosphere; Flow reactor; High pressure;
  • 70
  • [ 700-06-1 ]
  • [ 7498-57-9 ]
  • 3-(1H-indol-3-yl)-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
  • 71
  • [ 7498-57-9 ]
  • [ 1122-91-4 ]
  • (Z)-3-(p-bromophenyl)-2-(naphthalen-2-yl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With sodium methylate In methanol at 0 - 20℃; 2.2 Experimental procedure and spectroscopic data for (Z)-3-(p-bromophenyl)-2-(naphthalen-2-yl)acrylonitrile (2) To a solution of 2-naphtylacetonitrile (1.6g, 9.56mmol) and 4-bromobenzaldehyde (1.77g, 9.56mmol) in 30mL of anhydrous MeOH, was added sodium methoxide (650mg, 12.03mmol). The mixture was stirred for 15min at 0°C then warmed to room temperature with stirring overnight. The resulting precipitate was filtered, washed with 10mL of MeOH, then with 50mL of water, and dried. Compound ( 2) was obtained as a white solid in 77% yield; Rf=0.51 (cyclohexane/EtOAc, 95:05); m.p=47-49°C; 1H NMR (300MHz, CDCl3): δ (ppm): 7.44-7.65 (m, 5H), 7.72-7.83 (m, 3H), 7.86-7.94 (m, 3H), 8.19 (s, 1H, Hvinyl); 13C NMR (75MHz, CDCl3): δ (ppm): 112.1 (C), 117.1 (CN), 121.8 (CH), 124.3 (C), 125.9 (CH), 126.5 (CH), 126.6 (CH), 127.1 (CH), 127.9 (CH), 128.4 (CH), 130.1 (2CH), 130.9 (C), 131.7 (2CH), 132.2 (C), 132.8 (C), 133.0 (C), 140.0 (CH).
  • 72
  • [ 67843-74-7 ]
  • [ 7498-57-9 ]
  • [ 104-15-4 ]
  • [ 923982-65-4 ]
YieldReaction ConditionsOperation in experiment
72.2% Stage #1: (S)-epichlorohydrin; 2-naphthaleneacetonitrile With sodium t-butanolate In tetrahydrofuran at -25 - 0℃; for 2h; Inert atmosphere; Stage #2: With sodium tetrahydroborate; zinc(II) chloride In tetrahydrofuran at 55 - 65℃; for 12h; Stage #3: toluene-4-sulfonic acid Further stages; 1; 2; 5; 6; 9; 10; 11; 12 Synthesis of (1R, 2S) -2-hydroxymethyl-1-naphthyl-cyclopropanecarbonitrile Under a nitrogen atmosphere, sodium tert-butoxide (20.11 g, 209.3 mmol) was added to anhydrous tetrahydrofuran (40 mL), and the solution cooled to -25 to -15 ° C. was separately added to 2-naphthylacetonitrile (10 g, 10 g, 59.8 mmol) and (S) -epichlorohydrin (5.98 g, 71.8 mmol) were added to anhydrous tetrahydrofuran (60 mL), and the solution cooled to -10 to -5 ° C. was stirred at -10 to 0 ° C. The solution was slowly dropped while keeping After completion of the dropwise addition, the reaction mixture was stirred at -10 to 0 ° C. for 2 hours. The reaction mixture was used in the next step without quenching and purification. HPLC analysis indicated a mixture of diastereomers (6: 1 cis: trans).Example 12 FIG. Synthesis of (1S, 2R) -2-aminomethyl-2-naphthylene-2-ylcyclopropylmethanol tosylateUnder a nitrogen atmosphere, sodium borohydride (NaBH4) (9.05 g, 239.2 mmol) and zinc chloride (ZnCl2) (19.56 g, 143.5 mmol) were added to the reaction mixture solution of Example 11 while paying attention to foaming. After completion of the dropwise addition, the temperature was raised to 60 ° C. and stirred at 55 to 65 ° C. for 12 hours. The reaction solution was cooled to 5 ° C. or lower, and toluene (40 mL) was added. Separately, a solution prepared by diluting a 25% w / w aqueous sodium hydroxide solution (133.5 g, 956.8 mmol) with water (60 mL) was cooled to 0 to 5 ° C., and this was diluted with toluene. The solution was slowly added dropwise while maintaining the temperature at 30 ° C. or lower. After completion of the dropwise addition, the temperature was raised to 40 ° C. or higher, and the mixture was stirred for 30 minutes or longer to separate liquids. A solution obtained by diluting concentrated hydrochloric acid (12.1 g, 119.6 mmol) with water (50 mL) was added to the organic layer. After raising the temperature to 45 to 55 ° C., the mixture was stirred for 30 minutes or more, and after confirming that pH ≦ 2, liquid separation was performed. Water (40 mL) was added to the organic layer for liquid separation, and the organic layer was discarded. The obtained aqueous layers were combined and cooled to 20 ° C. or lower, and 25% w / w aqueous sodium hydroxide solution (20.9 g, 299 mmol) was added at 40 ° C. or lower and stirred, and it was confirmed that pH ≧ 11. Subsequently, toluene (70 mL) was added for liquid separation. The organic layer was washed with water (40 mL), and 70 mL of the organic solvent in the organic layer was distilled off under reduced pressure. 2-Methyltetrahydrofuran (60 mL) was added to the concentrated residue for dissolution, and p-toluenesulfonic acid monohydrate (10.8 g, 56.8 mmol) was added to the solution cooled to 10 ° C. or lower to precipitate crystals. After cooling, the precipitated crystals were collected by filtration, washed with 2-methyltetrahydrofuran (20 mL), and air-dried at 40 ° C. to give the title compound as a white to slightly yellow solid (33.54 g, total yield 72.2%, Chemical purity 98.0%, optical purity 95.6% ee).
  • 73
  • [ 109-04-6 ]
  • [ 7498-57-9 ]
  • C17H12N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-naphthaleneacetonitrile With potassium hydroxide In dimethyl sulfoxide at 60℃; Stage #2: 2-bromo-pyridine In dimethyl sulfoxide at 60 - 70℃; for 4h; 4.1.3. General procedure for synthesis of 3e-i and 3n-q General procedure: Appropriate starting arylacetonitrile (1 eq.) was added to a stirredsuspension of KOH (5 eq.) in DMSO (200 mL per 1 mol of KOH). Themixture was brought to 60 °C. Bromopyridine (1.5 eq.) was then addeddropwise, at 60-70 °C, followed by further stirring at this temperaturefor 4 h. The reaction mixture was cooled and poured onto water(500 mL) and the resulting cloudy solution was extracted with AcOEt(2 × 150 mL), washed with water (100 mL) and brine (100 mL). Theorganic extract was dried over anhydrous MgSO4, filtered and concentratedunder reduced pressure. The residue was dissolved in AcOH(100 mL) and concentrated H2SO4 (35 mL). The solution was heated at100 °C until TLC showed complete reaction (1-3 h). The solution wascooled and poured onto excess of ice-25% aqueous ammonia. The resultingmixture was extracted with CH2Cl2 (3 × 75 mL). The combinedorganic extracts were washed with water (2 × 75 mL), brine (75 mL),dried over anhydrous Na2SO4, filtered and evaporated. The title compoundswere purified by recrystallization or by FC.
  • 74
  • [ 7498-57-9 ]
  • [ 384-64-5 ]
  • C30H21F4N [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With lithium tert-butoxide In dimethyl sulfoxide at 80℃; for 12h; Inert atmosphere; 11 Example 11 Under a nitrogen atmosphere, add 0.2 mmol of 2-naphthylacetonitrile to a 25 ml reaction flask equipped with a reflux condenser,0.6 mmol of lithium tert-butoxide, 0.6 mmol of α-trifluoromethylstyrene, 4 ml of dimethyl sulfoxide, the reaction system was stirred at 80°C for 12 hours,Stop heating and stirring, cool to room temperature, add water to quench the reaction, add ethyl acetate to extract the reaction solution,The ethyl acetate layer was subjected to rotary evaporation under reduced pressure to remove the solvent, and then separated and purified by column chromatography to obtain the target product,The column chromatography eluent used was a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 30:1; the yield of the product was 75%.
  • 75
  • [ 13472-85-0 ]
  • [ 7498-57-9 ]
  • C18H14N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With potassium hydroxide In water at 45℃; for 48h;
  • 76
  • [ 7498-57-9 ]
  • [ 108-93-0 ]
  • [ 1390632-72-0 ]
YieldReaction ConditionsOperation in experiment
80% With potassium <i>tert</i>-butylate; C38H42Ir2N4O2 In neat (no solvent) at 120℃; for 1h; Inert atmosphere; Glovebox;
57% With carbonyl(pentamethylcyclopentadienyl)cobalt diiodide; ortho-diphenylphosphinobenzoic acid; potassium <i>tert</i>-butylate In toluene at 150℃; for 24h; Inert atmosphere;
  • 77
  • [ 7498-57-9 ]
  • [ 182163-96-8 ]
  • 2-(naphthalen-2-yl)-1-(3,4,5-trimethoxyphenyl)ethan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With [2,2]bipyridinyl; potassium fluoride; palladium diacetate; trifluoroacetic acid In tetrahydrofuran; water at 80℃; for 2h; Inert atmosphere; Schlenk technique; 4.2 General procedure for the synthesis of ketones (3a-r) General procedure: Under a nitrogen atmosphere, aryl acetonitrile 1 (3mmol), arylboronic acids 2 (6mmol), palladium acetate (5mol %), 2,2′-Bipyridine (10mol %), trifluoroacetic acid (30mmol), potassium fluoride (6mmol), tetrahydrofuran (20mL), and water (10mL) were successively added to a Schlenk reaction tube. The reaction mixture was stirred vigorously at 80°C for 2h. After the reaction mixture was cooled to room temperature, saturated sodium bicarbonate (30mL) was added into the solution, and the mixture was extracted with ethyl acetate (10mL) for 3 times. The combined organic layer was concentrated in vacuo. The residue was purified by flash column chromatography to afford desired product 3.
  • 78
  • [ 371-67-5 ]
  • [ 7498-57-9 ]
  • [ 57-66-9 ]
  • 4-(N,N-dipropylsulfamoyl)-N-[2-(naphthalen-2-yl)acetyl]-N-(2,2,2-trifluoroethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With copper(l) iodide In toluene at 40℃; for 12h; Solid Nitriles Using Pre-synthesized CF3CHN2; Method B General procedure: To a glass tube equipped with a magnetic stir bar were added drug acid (0.25 mmol, 1.0 equiv), CuI (2.4 mg, 0.0125 mmol, 0.05 equiv),and nitrile (solid, 5.0 mol, 20.0 equiv), then CF3CHN2 (in toluene, 0.85M/L, 0.6 mL) was added. The mixture was stirred at r.t. for 12 h. After the reaction was complete (monitored by TLC), the solvent was evaporated, and the residue was purified by chromatography (PE/EtOAc =25:1 to 2:1) to afford the desired products.
  • 79
  • [ 7498-57-9 ]
  • [ 4086-15-1 ]
  • [ 27869-60-9 ]
YieldReaction ConditionsOperation in experiment
69% With dichloro bis(acetonitrile) palladium(II); cesium hydroxide; potassium acetate In cyclohexane; toluene at 110℃; for 24h;
  • 80
  • [ 7498-57-9 ]
  • [ 137-07-5 ]
  • [ 1394973-45-5 ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: 2-naphthaleneacetonitrile; 2-amino-benzenethiol With aluminum (III) chloride at 90℃; for 0.166667h; Schlenk technique; Stage #2: With potassium phosphate; iodine; potassium iodide In N,N-dimethyl-formamide at 90℃; for 12h; Schlenk technique; General procedure for the synthesis of 2-acylbenzothiazoles General procedure: A 25 mL schlenk-flask was equipped with a magnetic stir bar and charged with substituted 2-aminobenzenethiols 1 (0.5 mmol, 1.0 equiv.), aryl-substituted acetonitriles 2 (1.5 mmol), AlCl3 (0.6 mmol) at 90 °C for 10 minutes, and then added I2 (0.6 mmol), KI (0.75 mmol), K3PO4 (0.5 mmol) and DMF (2 mL), stirred for 12 h. Then the reaction was quenched with 5% aqueous Na2S2O3 (20 mL) and extracted with CH2Cl2 (3×20 mL). The organic layer was dried over anhydrous Na2SO4, concentrated. The residue was purified by column chromatography using a mixture of EtOAc and petroleum ether as the eluent to afford product 3.
  • 81
  • [ 592-41-6 ]
  • [ 7498-57-9 ]
  • [ 201230-82-2 ]
  • C19H21N [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With acetylacetonatobis(ethylene)rhodium(I); hydrogen; C56H44N4O6P2; sodium hydroxide at 100℃; for 2h; Autoclave; 6 The preparation steps are as follows:In the air, add rhodium precursor acetylacetonyl bis(ethylene) rhodium Rh(acac)(CH2=CH2)2(1.8mmol%) into the autoclave,Phosphine ligand (3.6mmol%) as shown in formula (L7),Naphthaleneacetonitrile (1mmol),1-hexene (1mmol),NaOH (1mmol%) and solvent n-tridecane (3mL),Charge CO and H2=1:1, a total of 4MPa.The reaction was stirred at 100°C for 2h.After the reaction was completed, it was cooled to room temperature.After separation, a colorless and transparent liquid was obtained with a yield of 27%.
  • 82
  • [ 7498-57-9 ]
  • [ 107-18-6 ]
  • C15H15NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium carbonate In toluene at 75℃; for 2h; Inert atmosphere;
  • 83
  • [ 7498-57-9 ]
  • [ 104-54-1 ]
  • C21H19NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium <i>tert</i>-butylate In toluene at 80℃; for 4h; Inert atmosphere;
  • 84
  • [ 598-32-3 ]
  • [ 7498-57-9 ]
  • C16H17NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium <i>tert</i>-butylate In isopropyl alcohol; toluene at 80℃; for 12h;
  • 85
  • [ 7498-57-9 ]
  • [ 61619-02-1 ]
  • C25H21NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium <i>tert</i>-butylate In isopropyl alcohol; toluene at 80℃; for 12h;
Same Skeleton Products
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